Petersenjokumsen0030

Cortical spreading depolarization (CSD) is a propagating wave of tissue depolarization characterized by a large increase of extracellular potassium concentration and prolonged subsequent electrical silencing of neurons. Waves of CSD arise spontaneously in various acute neurological settings, including migraine aura and ischemic stroke. Recently, we have reported that pan-inhibition of adrenergic receptors (AdRs) facilitates the normalization of extracellular potassium after acute photothrombotic stroke in mice. Here, we have extended that mechanistic study to ask whether AdR antagonists also modify the dynamics of KCl-induced CSD and post-CSD recovery in vivo. Spontaneous neural activity and KCl-induced CSD were visualized by cortex-wide transcranial Ca2+ imaging in G-CaMP7 transgenic mice. AdR antagonism decreased the recurrence of CSD waves and accelerated the post-CSD recovery of neural activity. Two-photon imaging revealed that astrocytes exhibited aberrant Ca2+ signaling after passage of the CSD wave. This astrocytic Ca2+ activity was diminished by the AdR antagonists. Furthermore, AdR pan-antagonism facilitated the normalization of the extracellular potassium level after CSD, which paralleled the recovery of neural activity. These observations add support to the proposal that neuroprotective effects of AdR pan-antagonism arise from accelerated normalization of extracellular K+ levels in the setting of acute brain injury.Drug repositioning refers to new uses for existing drugs outside the scope of the original medical indications. This approach fastens the process of drug development allowing finding effective drugs with reduced side effects and lower costs. Colorectal cancer (CRC) is often diagnosed at advanced stages, when the probability of chemotherapy resistance is higher. Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, highly metastatic and difficult to treat. For both tumor types, available treatments are generally associated to severe side effects. In our work, we explored the effect of combining metformin and propranolol, two repositioned drugs, in both tumor types. We demonstrate that treatment affects viability, epithelial-mesenchymal transition and migratory potential of CRC cells as we described before for TNBC. We show that combined treatment affects different steps leading to metastasis in TNBC. Moreover, combined treatment is also effective preventing the development of 5-FU resistant CRC. Silmitasertib Our data suggest that combination of metformin and propranolol could be useful as a putative adjuvant treatment for both TNBC and CRC and an alternative for chemo-resistant CRC, providing a low-cost alternative therapy without associated toxicity.We analyze, using experiments and 3D MHD numerical simulations, the dynamic and radiative properties of a plasma ablated by a laser (1 ns, 10[Formula see text]-10[Formula see text] W/cm[Formula see text]) from a solid target as it expands into a homogeneous, strong magnetic field (up to 30 T) that is transverse to its main expansion axis. We find that as early as 2 ns after the start of the expansion, the plasma becomes constrained by the magnetic field. As the magnetic field strength is increased, more plasma is confined close to the target and is heated by magnetic compression. We also observe that after [Formula see text] ns, the plasma is being overall shaped in a slab, with the plasma being compressed perpendicularly to the magnetic field, and being extended along the magnetic field direction. This dense slab rapidly expands into vacuum; however, it contains only [Formula see text] of the total plasma. As a result of the higher density and increased heating of the plasma confined against the laser-irradiated solid target, there is a net enhancement of the total X-ray emissivity induced by the magnetization.Symptoms of autonomic dysfunction are common in Fabry disease. In this study we aimed to evaluate alterations in the pupillary response to white light stimulation in patients with Fabry disease and their association with the severity of autonomic symptoms. Fourteen consecutive patients with Fabry disease and 14 healthy control participants were enrolled in this cross-sectional study. The Mainz Severity Score Index (MSSI) was used to measure the severity of Fabry disease and the Composite Autonomic Symptom Scale 31 (COMPASS 31) questionnaire was used to evaluate the severity of autonomic symptoms. The pupil light responses were assessed with an infrared dynamic pupillometry unit. There were significant reductions in the amplitude (P = 0.048) and duration (P = 0.048) of pupil contraction, and the latency of pupil dilation (P = 0.048) in patients with Fabry disease compared to control subjects. The total weighted COMPASS 31 score correlated with MSSI (r = 0.592; P = 0.026) and the duration of pupil dilation (ρ = 0.561; P = 0.037). The pupillomotor weighted sub-score of the COMPASS 31 correlated inversely with the duration of pupil contraction (r = - 0.600; P = 0.023) and latency of pupil dilation (ρ = - 0.541; P = 0.046), and directly with the duration of pupil dilation (ρ = 0.877; P  less then  0.001) and MSSI (r = 0.533; P = 0.049). In conclusion, abnormal pupillary function is demonstrated in patients with Fabry disease, which is associated with the severity of autonomic symptoms.The sustainable expansion of steam-assisted gravity drainage, as one of the most popular enhanced oil recovery methods, strongly depends on the proper management of the produced water. The strict environmental regulations have forced the oil sands industry to treat and reuse the produced water for oil extraction. Membrane separation as a single-step water treatment technique has played an important role in removing multiple-sized contaminants from wastewater. However, fouling limits the widespread application of this technology if the membrane is not modified properly to achieve antifouling propensities. Herein, we used the layer-by-layer assembly technique to sequentially coat the hydrophilic poly(diallyl dimethylammonium chloride) and polyacrylic acid on the surface of the polyamide-imide porous membrane to improve its fouling resistance. The effect of the number of bilayers on fouling and permeation properties was examined. The membrane with the highest fouling resistance and reasonable hydrodynamic permeability of 5.2 LMH/psi was achieved by coating four bilayers. This membrane exhibited a low flux decline of 50.2% and a high flux recovery ratio of 100%, while these numbers for the pristine PAI membrane were 75.9% and 97.8% under similar test conditions. The enhanced antifouling characteristics of the modified membranes indicate the viability of these membranes for oil sands produced water treatment with an easy cleaning procedure. The key parameter that contributed to the enhanced fouling resistance of the bilayer-coated membranes was the improved surface hydrophilicity, which manifests through the reduction of water contact angle from 62° ± 3° for the pristine membrane to 52° ± 2° for surface-modified membranes.Mass-flowering crop monocultures, like sunflower, cannot harbour a permanent pollinator community. Their pollination is best secured if both managed honey bees and wild pollinators are present in the agricultural landscape. Semi-natural habitats are known to be the main foraging and nesting areas of wild pollinators, thus benefiting their populations, whereas crops flowering simultaneously may competitively dilute pollinator densities. In our study we asked how landscape structure affects major pollinator groups' visiting frequency on 36 focal sunflower fields, hypothesising that herbaceous semi-natural (hSNH) and sunflower patches in the landscape neighbourhood will have a scale-dependent effect. We found that an increasing area and/or dispersion of hSNH areas enhanced the visitation of all pollinator groups. These positive effects were scale-dependent and corresponded well with the foraging ranges of the observed bee pollinators. In contrast, an increasing edge density of neighbouring sunflower fields resulted in considerably lower visiting frequencies of wild bees. Our results clearly indicate that the pollination of sunflower is dependent on the composition and configuration of the agricultural landscape. We conclude that an optimization of the pollination can be achieved if sufficient amount of hSNH areas with good dispersion are provided and mass flowering crops do not over-dominate the agricultural landscape.We developed a novel method for production of no-carrier-added (n.c.a.) [188, 189, 191Pt]PtIICl42- from an Ir target material, and then synthesized n.c.a. [*Pt]cis-[PtIICl2(NH3)2] ([*Pt]cisplatin) from [*Pt]PtIICl42-. [*Pt]PtIICl42- was prepared as a synthetic precursor of n.c.a. *Pt complex by a combination of resin extraction and anion-exchange chromatography after the selective reduction of IrIVCl62- with ascorbic acid. The ligand-substitution reaction of Cl with NH3 was promoted by treating n.c.a. [*Pt]PtIICl42- with excess NH3 and heating the reaction mixture, and n.c.a. [*Pt]cisplatin was successfully produced without employing precipitation routes. After this treatment, [*Pt]cisplatin was isolated through preparative HPLC with a radiochemical purity of 99 + % at the end of synthesis (EOS).Lipidome-wide metabolites may be useful biomarkers of pregnancy outcomes. We sought to characterize maternal lipidomic signatures associated with preterm birth and neonatal anthropometric parameters. Plasma samples were collected 24-28 weeks gestation, and lipidomic profiling was quantified using high-performance liquid chromatography tandem mass spectrometry. Lipid metabolites were analyzed individually and as whole lipid classes and subgroups based on degree of hydrocarbon chain saturation. Associations were estimated using linear and logistic regression. After false discovery adjustment (q  less then  0.15), four plasmenyl-phosphatidylethanolamines and three free fatty acids associated with increased risk for spontaneous preterm birth. Five phosphatidylinositols, two phosphatidylglycerols, and one phosphatidic acid were associated with large for gestational age neonates. The saturated plasmenyl-phosphatidylethanolamines held the association with increased risk for spontaneous preterm birth. Both the mono- and poly-unsaturated free fatty acids held the association for increased risk for spontaneous preterm birth. Mono- and poly-unsaturated phosphatidylinositols were associated with large for gestational age neonates. Whole lipid classes (plasmenyl-phophatidylcholines and plasmenyl-phosphatidylethanolamines) were associated with increased risk for large for gestational age at delivery. This study provides evidence that finer omics-scale analysis of the maternal lipidome may be more informative biomarkers of pregnancy outcomes compared to whole class level lipid analysis.This population-based retrospective cohort study investigated the prevalence of myopia among patients with Type 1 and Type 2 diabetes mellitus (DM) and evaluate risk factors for myopia in these groups. Records from 2000 to 2012 with at least one year of follow-up from the Taiwan National Health Insurance Research Database were included. This study included 35,538 patients with DM and 71,076 patients without DM. Patients with DM had a significantly higher adjusted hazard ratio for myopia in all age groups and both sexes compared with patients without DM. The subgroup analysis results revealed that the rates of myopia and astigmatism were significantly higher among patients with DM compared with patients without DM aged  less then  60 years. However, the rates of high myopia or myopia progression to high myopia did not differ significantly between the two groups. These findings indicate that DM is a critical risk factor for myopia and astigmatism among patients aged  less then  60 years. Therefore, active surveillance and earlier treatment of myopia are critical for patients with DM.